Klaus R. Liedl

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The imminent threat of influenza pandemics and repeatedly reported emergence of new drug-resistant influenza virus strains demonstrate the urgent need for developing innovative and effective antiviral agents for prevention and treatment. At present, influenza neuraminidase (NA), a key enzyme in viral replication, spread, and pathogenesis, is considered to(More)
The structure of human Janus kinase 2 (JAK2) comprising the two C-terminal domains (JH1 and JH2) was predicted by application of homology modelling techniques. JH1 and JH2 represent the tyrosine kinase and tyrosine kinase-like domains, respectively, and are crucial for function and regulation of the protein. A comparison between the structures of the two(More)
The prediction of blood-brain barrier permeation is vitally important for the optimization of drugs targeting the central nervous system as well as for avoiding side effects of peripheral drugs. Following a previously proposed model on blood-brain barrier penetration, we calculated the cross-sectional area perpendicular to the amphiphilic axis. We obtained(More)
Blockade of the N-methyl-D-aspartate receptor by uncompetitive antagonists has implications for symptomatic and neuroprotective therapy of various neuropsychiatric diseases. Since the three-dimensional (3D) structure of this ion channel is unknown, the structural requirements for uncompetitive inhibition were investigated by application of a three-step(More)
Protein-protein interfaces have crucial functions in many biological processes. The large interaction areas of such interfaces show complex interaction motifs. Even more challenging is the understanding of (multi)specificity in protein-protein binding. Many proteins can bind several partners to mediate their function. A perfect paradigm to study such(More)
BACKGROUND Cav1.3 voltage-gated L-type calcium channels (LTCCs) are part of postsynaptic neuronal signaling networks. They play a key role in brain function, including fear memory and emotional and drug-taking behaviors. A whole-exome sequencing study identified a de novo mutation, p.A749G, in Cav1.3 α1-subunits (CACNA1D), the second main LTCC in the brain,(More)
Investigations of spontaneous, i.e. not forced, B-DNA's B(I)<==>B(II) substate transitions are carried out on the d(CGCGAATTCGCG)2 EcoRI dodecamer sequence using Molecular Dynamics Simulations. Analysis of the resulting transition processes with respect to the backbone angles reveals concerted changes not only for backbone angles epsilon, zeta, and beta,(More)
At present, neuraminidase (NA) inhibitors are the mainstay of pharmacological strategies to fight against global pandemic influenza. In the search for new antiviral drug leads from nature, the seed extract of Alpinia katsumadai has been phytochemically investigated. Among the six isolated constituents, four diarylheptanoids showed in vitro NA inhibitory(More)
Many approaches to studying protein-ligand interactions by computational docking are currently available. Given the structures of a protein and a ligand, the ultimate goal of all docking methods is to predict the structure of the resulting complex. This requires a suitable representation of molecular structures and properties, search algorithms to(More)